Well for processing a fluid

ABSTRACT

A well ( 50 ) comprising a side wall ( 10 ), a sealing ring ( 40 ), a rib arrangement ( 5 ), and a filter ( 20 ), for use in processing a fluid, e.g., by microtitration or microfiltration, is disclosed.

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

[0001] This patent application claims the benefit of U.S. ProvisionalPatent Application No. 60/294,211, filed May 31, 2001.

FIELD OF THE INVENTION

[0002] This invention relates to wells for use in processing fluids,e.g., by titration and/or filtration, and more preferably relates tomultiwell microtitration and microfiltration devices.

BACKGROUND OF THE INVENTION

[0003] Multiple well test devices are used in a variety ofmicrotitration and/or microfiltration protocols. Typically, the deviceshave a standard number of wells, e.g., 96 wells, or 384 wells (arrangedin four blocks of 96 wells each), and the wells include a filterarranged such that application of a vacuum or air pressure to one sideof the device causes the fluid in each well to pass through the filter.

[0004] When the device is used in for microtitration, e.g., for animmunoassay or a hybridization assay, the filter is generally used tosupport one or more components of the assay, such as an antigen,antibody, nucleic acid probe or nucleic acid sample. A supportedcomponent (e.g., a specific binding agent) binds to an unsupportedcomponent in a fluid sample. At least one component can be contained in,on, and/or through the filter, e.g., by physical entrapment, chemicalbinding and/or adsorption.

[0005] When used for microfiltration the filter is generally used toremove one or more components from solutions passed through it, e.g., onthe basis of physical, biological and/or chemical interactions in or onthe filter. The interactions can be, for example, between the filter andthe component to be retained, or between one or more materials retainedin or on the filter and the component to be retained.

[0006] Accordingly, the devices can be utilized to remove one or moreundesirable and/or desirable materials from a fluid. For example, thedevices can be used to remove particulates from a sample before furtherprocessing (e.g., analysis) of the sample and/or to retain a desiredligand for later recovery and further processing.

[0007] Some conventional devices are labor intensive to manufactureand/or are not adapted for use with a variety of filters. Additionally,the seal of the filter in the device can be adversely affected byhandling and/or fluid processing conditions.

[0008] The present invention provides for ameliorating at least some ofthe disadvantages of the prior art. These and other advantages of thepresent invention will be apparent from the description as set forthbelow.

BRIEF SUMMARY OF THE INVENTION

[0009] In accordance with an embodiment of the invention, a well forprocessing fluid is provided, the well comprising a hollow tubecomprising a side wall having an inner surface, a bottom end comprisinga bottom wall and a fluid flow port, and a rib arrangement projectingupwardly from the bottom wall, the rib arrangement having a top surfacespaced away from the inner surface of the side wall; a sealing ringhaving an outer surface and a bottom surface, the outer surface of thesealing ring pressing against the inner surface of the side wall; and afilter comprising at least one filter element, the filter having anupper surface and a lower surface, the filter being compressed betweenthe bottom surface of the sealing ring and the top surface of the ribarrangement. Typically, the bottom surface of the sealing ring pressesagainst the upper surface of the filter while the top surface of the ribarrangement presses against the lower surface of the filter. In apreferred embodiment of the well, the bottom surface of the sealing ringhas a width that is at least the width of the top surface of the ribarrangement.

[0010] In accordance with another embodiment, a well for processingfluid is provided, the well comprising a hollow tube comprising a sidewall having an inner surface and an inwardly extending lip having alower surface; a bottom end comprising a bottom wall and a fluid flowport, and a sealing ring comprising a rib arrangement projectingupwardly from the bottom wall, the rib arrangement having a top surface;the sealing ring also comprising an outer surface, the outer surface ofthe sealing ring pressing against the inner surface of the side wall;and a filter comprising at least one filter element, the filter havingan upper surface and a lower surface, the filter being compressedbetween the lower surface of the lip and the top surface of the ribarrangement. Typically, the top surface of the rib arrangement is spacedaway from the inner surface of the side wall. Preferably, the lowersurface of the lip has a width that is at least the width of the topsurface of the rib arrangement.

[0011] A well for processing fluid according to another embodiment ofthe invention comprises a hollow tube comprising a side wall having aninner surface and an inwardly extending lip, the lip having a ribarrangement projecting downwardly from the lip, the rib arrangementhaving a bottom surface; a bottom end comprising a bottom wall and afluid flow port and a sealing ring comprising an outer surface and a topsurface, the outer surface of the sealing ring pressing against theinner surface of the side wall of the tube, and a filter comprising atleast one filter element, the filter having an upper surface and a lowersurface, the filter being compressed between the top surface of thesealing ring and the bottom surface of the rib arrangement.

[0012] In some embodiments of the well, the bottom end also includes adrainage grid comprising at least one drainage channel communicatingwith the fluid flow port. For example, the bottom end can include adrainage grid comprising a plurality of drainage grid spacers projectingupwardly from the bottom wall, wherein a plurality of drainage channelsare provided between the drainage grid spacers, and the drainagechannels communicate with the fluid flow port.

[0013] In accordance with another embodiment, a plurality of the wellsare connected together to provide a multiple well device, e.g., in theform of a 96 or 384 well device, in some embodiments, a 96 or 384 welltray.

[0014] Methods are also provided for processing a fluid utilizingembodiments of the well and the multiple well devices. Suitable methodsinclude, for example, microtitration, microfiltration, and microcultureprocedures.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015]FIG. 1 shows a top view of an embodiment of a base suitable foruse in a multiple well device according to the present invention,showing a first well including filter and a sealing ring, a second wellincluding a rib arrangement and fluid flow port, and a third wellincluding a rib arrangement, a drainage grid, and a fluid flow port.

[0016]FIG. 2 shows a partial cross-sectional view of a portion of thebase including the third well shown in FIG. 1, showing the inner surfaceof the side wall of the well, the bottom wall of the well, as well asthe rib arrangement and the drainage grid projecting upwardly from thebottom wall.

[0017]FIG. 3 shows an enlarged top view of the third well shown in FIG.1, the well including the rib arrangement, the drainage grid, and thefluid flow port.

[0018]FIG. 4 shows an embodiment of a sealing ring. FIG. 4a shows a topview, and FIG. 4b shows a cross-section view along lines 4 b-4 b in FIG.4a.

[0019]FIG. 5 shows partial cut away views of a portion of a wellaccording to an embodiment of the invention, showing a sealing ring, afilter, a rib arrangement, and a drainage grid. FIG. 5a shows anexploded view, and FIG. 5b shows an assembled view wherein the sealingring is retained such that the outer surface of the sealing ring pressesagainst the inner surface of the side wall of the well, and the bottomsurface of the ring presses against the upper surface of the filterwhile the top surface of the rib arrangement presses against the lowersurface of the filter so that the filter is sealed in the well.

[0020]FIG. 6 shows a partial cross-sectional view of another embodimentof a multiple well device according to the invention, showing a topplate including a plurality of sealing rings, and a bottom plateincluding the bottom ends of a plurality of wells, wherein each endincludes a bottom wall, a fluid flow port, and a rib arrangementprojecting upwardly from the bottom wall, herein the sealing ring isretained such that the outer surface of the sealing ring presses againstthe inner surface of the side wall of the well, and the bottom surfaceof the ring presses against the upper surface of the filter while thetop surface of the rib arrangement presses against the lower surface ofthe filter so that the filter is sealed in the well.

[0021]FIG. 7 shows a top view of the bottom plate shown in FIG. 6,showing the bottom ends of a plurality of wells, wherein each endincludes a bottom wall, a fluid flow port, and a rib arrangementprojecting upwardly from the bottom wall.

[0022]FIG. 8 shows a top view of the bottom plate including the bottomend of one of the wells shown in FIG. 6, showing a bottom wall, a ribarrangement, and a fluid flow port.

[0023]FIG. 9 shows a top view of the top plate shown in FIG. 6.

[0024]FIG. 10 shows partial cross-sectional views of the plates shown inFIG. 6. FIG. 10a shows a partial cross-sectional view of the top plate,and FIG. 10b shows a partial cross-sectional view of the bottom plate.

[0025]FIG. 11 shows a partial cross-sectional view of another embodimentof a multiple well device according to the invention, showing anassembled well and an exploded view of a well. The Figure shows a topplate including inwardly extending lips, wherein each lip has a bottomsurface; and individual lower chambers, each chamber including thebottom end of a well, wherein each bottom end includes a bottom wall, afluid flow port, and a sealing ring comprising a rib arrangementprojecting upwardly from the bottom wall, wherein the sealing ring isretained such that the outer surface of the sealing ring presses againstthe inner surface of the side wall of the well, and the bottom surfaceof the lip presses against the upper surface of the filter while the topsurface of the rib arrangement presses against the lower surface of thefilter, so that the filter is sealed in the well.

[0026]FIG. 12 shows a cut away view of the lower chamber of one of thewells shown in FIG. 11, showing the bottom end of the well, including abottom wall, a fluid flow port, and a sealing ring comprising a ribarrangement projecting upwardly from the bottom wall.

[0027]FIG. 13 shows a top view of the bottom end of the well shown inFIG. 11, showing a bottom wall, a rib arrangement, a drainage grid, anda fluid flow port.

[0028]FIG. 14 shows a top view of the top plate shown in FIG. 11.

[0029]FIG. 15 shows a partial cross-sectional view of the top plateshown in FIG. 14.

[0030]FIG. 16 shows a partial cross-sectional view of another embodimentof a multiple well device according to the invention, showing anassembled well and an exploded view of a well. The Figure shows a topplate including inwardly extending lips, wherein each lip has a ribarrangement projecting downwardly from the lip; and individual lowerchambers, each chamber including the bottom end of a well, wherein eachbottom end includes a bottom wall, a fluid flow port, and a sealing ringhaving an outer surface and a top surface, wherein the sealing ring isretained such that the outer surface of the sealing ring presses againstthe inner surface of the side wall of the well, and the bottom surfaceof the rib arrangement presses against the upper surface of the filterwhile the top surface of the sealing ring presses against the lowersurface of the filter, so that the filter is sealed in the well.

[0031]FIG. 17 shows a top view of the bottom end of the well shown inFIG. 16, showing a bottom wall, a drainage grid, and a fluid flow port.

[0032]FIG. 18 shows a cut away view of the lower chamber of one of thewells shown in FIG. 16, showing the bottom end of the well, including abottom wall, a fluid flow port, and a sealing ring.

[0033]FIG. 19 shows a partial cross-sectional view of the top plateshown in FIG. 16.

DETAILED DESCRIPTION OF THE INVENTION

[0034] In one embodiment of the present invention, a well for use inprocessing a fluid comprises a hollow tube having an axis, the tubecomprising a side wall having an inner surface; upper and lower axiallyspaced ends, the lower end comprising a bottom wall and a fluid flowport, and a rib arrangement projecting upwardly from the bottom wall,the rib arrangement having a top surface spaced from the inner surfaceof the side wall; a sealing ring having an outer surface and a bottomsurface, the outer surface of the sealing ring pressing against theinner surface of the side wall; and a filter comprising at least onefilter element, the filter having a upper surface and a lower surface,the filter being compressed between the bottom surface of the sealingring and the top surface of the rib arrangement. Preferably, the bottomsurface of the sealing ring has a radial width that is at least theradial width of the top surface of the rib arrangement. Typically, thesealing ring seals the filter against the rib arrangement wherein thebottom surface of the sealing ring presses against the upper surface ofthe filter while the top surface of the rib arrangement presses againstthe lower surface of the filter. In some embodiments, the sealing ringhas a hollow bore suitable for receiving fluid, wherein the boresubstantially extends to the upper end of the tube.

[0035] A well for use in processing a fluid according to anotherembodiment of the invention comprises a hollow tube having an axis, thetube comprising a side wall having an inner surface; upper and loweraxially spaced ends, the lower end comprising a bottom wall, a fluidflow port, a drainage grid arrangement comprising at least one drainagegrid spacer projecting upwardly from the bottom wall, and a ribarrangement projecting upwardly from the bottom wall, the ribarrangement having a top surface spaced from the inner surface of theside wall of the tube; a filter comprising at least one filter element,the filter having an upper surface and a lower surface; and a sealingring sealing the filter against the rib arrangement, the sealing ringhaving an outer surface, and a bottom surface, the bottom surface havinga radial width that is at least the radial width of the top surface ofthe rib arrangement, the outer surface of the sealing ring pressingagainst the inner surface of the side wall of the tube, and the bottomsurface of the ring pressing against the upper surface of the filterwhile the top surface of the rib arrangement presses against the lowersurface of the filter.

[0036] In yet another embodiment of the present invention, a well foruse in processing a fluid comprises a hollow tube having an axis, thetube comprising a side wall having an inner surface and a lip extendinginwardly from the side wall, the lip having a lower surface; upper andlower axially spaced ends, the lower end comprising a bottom wall and afluid flow port, and a sealing ring comprising a rib arrangementprojecting upwardly from the bottom wall, the rib arrangement having atop surface; the sealing ring comprising an outer surface and the topsurface of the rib arrangement, the outer surface of the sealing ringpressing against the inner surface of the side wall; and a filtercomprising at least one filter element, the filter having a uppersurface and a lower surface, the filter being compressed between thelower surface of the lip and the top surface of the rib arrangement.Typically, the top surface of the rib arrangement is spaced from theinner surface of the side wall. Preferably, the top surface of the ribarrangement has a radial width that is at least the radial width of thelower surface of the lip. Typically, the sealing ring seals the filteragainst the rib arrangement wherein the top surface of the sealing ringpresses against the lower surface of the filter while the lower surfaceof the lip presses against the upper surface of the filter.

[0037] A well for use in processing a fluid according to anotherembodiment of the invention comprises a hollow tube having an axis, thetube comprising a side wall having an inner surface and a lip extendinginwardly from said side wall, the lip having a lower surface; upper andlower axially spaced ends, the lower end comprising a bottom wall and afluid flow port and a sealing ring comprising an outer surface and a topsurface, the outer surface of the sealing ring pressing against theinner surface of the side wall of the tube; a filter comprising at leastone filter element, the filter having an upper surface and a lowersurface, the filter being compressed between the top surface of thesealing ring and the lower surface of the lip. In a preferredembodiment, the lip comprises a rib arrangement projecting downwardlyfrom the lip, more preferably, wherein the rib arrangement has a bottomsurface spaced from the inner surface of the side wall, and the filteris compressed between the top surface of the sealing ring and the bottomsurface of the rib arrangement. In another embodiment, the sealing ringfurther comprises a rib arrangement projecting upwardly from the bottomwall, the rib arrangement having a top surface, wherein the filter iscompressed between the top surface of the rib arrangement and the lowersurface of the lip. The top surface of the rib arrangement can be spacedfrom the inner surface of the side wall.

[0038] In accordance with another embodiment, a microtitration ormicrofiltration device is provided comprising a well comprising a hollowtube having an axis, the tube comprising a side wall having an innersurface, upper and lower axially spaced ends, the lower end comprising abottom wall, a drainage grid comprising at least one drainage channel,and a fluid flow port, and a rib arrangement projecting upwardly fromthe bottom wall, the rib arrangement having a top surface that does notcontact the inner surface of the side wall of the tube, a filtercomprising at least one filter element, the filter having an uppersurface and a lower surface, and a sealing ring sealing the filteragainst the rib arrangement, the sealing ring having an outer surface,and a bottom surface, the bottom surface having a width that is at leastthe width of the top surface of the rib arrangement, the outer surfaceof the sealing ring pressing against the inner surface of the side wallof the tube, and the bottom surface of the ring pressing against theupper surface of the filter while the top surface of the rib arrangementpresses against the lower surface of the filter.

[0039] In accordance with another embodiment, a device for culturing acell suspension or tissue comprises a well for receiving a cellsuspension or tissue, the well having a side wall having an innersurface, a bottom end comprising a bottom wall and a fluid flow port,and a rib arrangement projecting upwardly from the bottom wall, the ribarrangement having a top surface that does not contact the inner surfaceof the side wall; a filter sealed in the well, the filter comprising atleast one filter element suitable for culturing the cell suspension ortissue, the filter having a upper surface and a lower surface; and asealing ring sealing the filter against the rib arrangement, the sealingring having an outer surface, and a bottom surface, the bottom surfacehaving a width that is at least the width of the top surface of the ribarrangement, the sealing ring pressing against the inner surface of theside wall, and the bottom surface of the ring pressing against the uppersurface of the filter while the top surface of the rib arrangementpresses against the lower surface of the filter. Typically, devicefurther comprises a culture medium contained in the well.

[0040] In more preferred embodiments of the invention, a plurality ofwells are connected together to provide a multiple well device. Inaccordance with embodiments of the invention, the potential forcross-contamination from one well to another can be eliminated.

[0041] An embodiment of a multiple well device according to theinvention comprises a plurality of wells for receiving liquid samples tobe processed, each well having a side wall having an inner surface, abottom end comprising a bottom wall and a fluid flow port, and a ribarrangement projecting upwardly from the bottom wall, the ribarrangement having a top surface spaced from the inner surface of theside wall; a sealing ring having an outer surface, and a bottom surface,the outer surface of the sealing ring pressing against the inner surfaceof the side wall of the tube; and a filter comprising at least onefilter element, the filter having a upper surface and a lower surface,the filter being compressed between the bottom surface of the sealingring and the top surface of the rib arrangement.

[0042] In another embodiment, a multiple well device comprises aplurality of wells for receiving liquid samples to be processed, eachwell comprising a side wall having an inner surface, a bottom endcomprising a bottom wall and a fluid flow port, and a rib arrangementprojecting upwardly from the bottom wall, the rib arrangement having atop surface that does not contact the inner surface of the side wall; afilter comprising at least one filter element, the filter having a uppersurface and a lower surface; and a sealing ring sealing the filteragainst the rib arrangement, the sealing ring having an outer surfaceand a bottom surface, the bottom surface having a width that is at leastthe width of the top surface of the rib arrangement, the outer surfaceof the sealing ring pressing against the inner surface of the side wall,and the bottom surface of the ring pressing against the upper surface ofthe filter while the top surface of the rib arrangement presses againstthe lower surface of the filter.

[0043] In some embodiments of multiple well devices according to theinvention, the device comprises at least a top plate and a bottom plate,wherein the top plate comprises the sealing ring, and the bottom platecomprises the bottom wall and the rib arrangement. In one embodimentwherein the top plate comprises the sealing ring, the sealing ring has ahollow bore that substantially extends to the top surface of the plate.

[0044] In accordance with another embodiment, a multiple well devicecomprises a plurality of wells for receiving liquid samples to beprocessed, each well comprising a side wall having an inner surface anda lip extending inwardly from the side wall, the lip having a lowersurface; a bottom end comprising a bottom wall and a fluid flow port andsealing ring comprising a rib arrangement projecting upwardly from thebottom wall, the rib arrangement having a top surface that does notcontact the inner surface of the side wall, the sealing ring comprisingan outer surface; and a filter comprising at least one filter element,the filter having a upper surface and a lower surface; the outer surfaceof the sealing ring pressing against the inner surface of the side wall;and the lower surface of the lip pressing against the upper surface ofthe filter while the top surface of the rib arrangement presses againstthe lower surface of the filter.

[0045] In accordance with an embodiment of the invention, a multiplewell device comprises a plurality of wells for receiving liquid samplesto be processed, each well comprising a side wall having an innersurface and a lip extending inwardly from the side wall, the lip havinga rib arrangement projecting downwardly from the lip, the ribarrangement having a bottom surface that does not contact the innersurface of the side wall; a bottom end comprising a bottom wall and afluid flow port and a sealing ring comprising an outer surface and a topsurface, wherein the bottom wall of the bottom end comprises the topsurface of the sealing ring; and a filter comprising at least one filterelement, the filter having a upper surface and a lower surface; theouter surface of the sealing ring pressing against the inner surface ofthe side wall; and the top surface of the sealing ring pressing againstthe lower surface of the filter while the bottom surface of the ribarrangement presses against the upper surface of the filter.

[0046] Another embodiment of a multiple well device according to theinvention comprises a top plate comprising the upper ends of a pluralityof wells; a plurality of separate inserts comprising the lower ends ofthe plurality of wells, each insert comprising a bottom wall and a fluidflow port; and a plurality of filters, each filter comprising at leastone filter element, wherein each filter is sealed between the top plateand an insert. In some embodiments, the top plate includes a pluralityof sealing rings, and in some other embodiments, each insert comprises asealing ring.

[0047] Yet another embodiment of a multiple well device according to theinvention comprises a bottom plate comprising the bottom ends of aplurality of wells, each bottom end comprising a bottom wall and a fluidflow port; a plurality of separate inserts comprising the upper ends ofthe plurality of wells; and a plurality of filters, each filtercomprising at least one filter element, wherein each filter is sealedbetween the top plate and an insert. In some embodiments, the bottomplate includes a plurality of sealing rings, and in some otherembodiments, each insert comprises a sealing ring.

[0048] Embodiments of multiple well devices include wells connectedtogether in the form of, for example, a strip, disc, or tray. Multiplewell devices can include integrally formed wells (e.g., formed byinjection or blow molding), or the wells can be formed from a pluralityof components, e.g., an upper plate, tray or insert defining the upperportion of the wells and/or the sealing ring, and a bottom plate, trayor insert defining at least the bottom wall of the wells.

[0049] The wells, and more preferably, the multiple well devices, aresuitable for use with a variety of other components such as a chamber,plenum, manifold, manifold cover, or the like, e.g., for applyingreduced pressure or vacuum to the wells. Accordingly, some embodimentsof the wells and multiple well devices further comprise, for example, amanifold cover.

[0050] Embodiments of methods for using the wells and multiple welldevices are also provided.

[0051] For example, one embodiment of a method for processing a fluidcomprises passing a fluid into a well comprising a side wall having aninner surface, and a bottom end having a rib arrangement having a topsurface, wherein the top surface of the rib arrangement is spaced fromthe inner surface of the side wall, and a fluid flow port; the wellhaving a filter comprising at least one filter element sealed therein,the filter being compressed between a lower surface of a sealing ring,and the top surface of the rib arrangement, and, passing at least aportion of the fluid through the filter and through the fluid flow portat the bottom end of the well.

[0052] In another embodiment, a method for processing a fluid comprisespassing a fluid into a device comprising a well comprising a side wallhaving an inner surface, and a lip extending inwardly from said sidewall, the lip having a lower surface; and lower end comprising a bottomwall and a fluid flow port and a sealing ring, the sealing ringcomprising a top surface; the well having a filter comprising at leastone filter element sealed therein, the filter being compressed between alower surface of the lip, and the top surface of the sealing ring, and,passing at least a portion of the fluid through the filter and throughthe fluid flow port at the bottom end of the well.

[0053] Preferably, the method comprises processing fluid in a multiplewell device, wherein fluid is passed into a plurality of wells asdescribed above.

[0054] Embodiments of the method can include binding at least onecomponent in the fluid to be processed to at least one binding agent inthe well, in some embodiments, binding at least one component in thefluid to be processed to at least one binding agent in or on the filter.For example, embodiments of the method can include antigen-antibodybinding, binding a nucleic acid in a sample to a complementary nucleicacid probe, binding ligands, and binding proteins. In some embodiments,at least one binding agent is a specific binding agent such as amonoclonal antibody or a nucleic acid probe that specifically binds to acomponent in the fluid to be processed. Other embodiments of the methodinclude, for example, removing particulates from the fluid to beprocessed, and synthesizing desired materials in the wells. If desired,embodiments of the method also include analyzing the filtrate passingthrough the filter and/or analyzing the bound component (in someembodiments, after cleaving the bound component from the well).

[0055] Each of the components of the invention will now be described inmore detail below, wherein like components have like reference numbers.

[0056]FIG. 1 shows a top view of a multiple well device 100 according toan embodiment of the invention, comprising a base or bottom plate 101suitable for providing the bottom ends for a plurality of wells. FIG. 1also shows an assembled well 50 according to an embodiment of theinvention, as well as two non-assembled wells 51 and 52. Assembled well50 comprises a side wall 10, a sealing ring 40, and a filter 20. Whilenot shown in assembled well 50, the two non-assembled wells 51 and 52show a bottom end 3, comprising a rib arrangement 5 and a fluid flowport 7 (all covered by filter 20 in the assembled well 50), and a sidewall 10. Non-assembled well 52 also shows a drainage grid 80, as well asthe rib arrangement 5.

[0057]FIG. 2 shows a partial cross-sectional view of a portion of thebottom plate 101 including the non-assembled well 52 shown in FIG. 1,showing the side wall 10 having an inner surface 2, and the bottom end3, comprising a bottom wall 4, a rib arrangement 5 projecting upwardlyfrom the bottom wall, the rib arrangement having a top surface 6, adrainage grid 80, and a fluid flow port 7.

[0058]FIG. 3 shows a top view of the non-assembled well 52 shown in FIG.2, showing the side wall 10 having an inner surface 2, and the bottomend 3, comprising a bottom wall 4, a rib arrangement 5 having a topsurface 6, a drainage grid 80, and a fluid flow port 7.

[0059]FIG. 4 shows an embodiment of a sealing ring 40. FIG. 4a shows atop view of sealing ring 40 having an outer surface 43, and FIG. 4bshows a cross-section view along lines 4 b-4 b in FIG. 4a, showing thetop surface 42, the bottom surface 41, and the outer surface 43 ofsealing ring 40.

[0060] The separate and/or partially assembled components shown in FIGS.1-4 are shown arranged in FIGS. 5a (exploded view) and 5 b (assembledview), that illustrate a partial cut away view of a device comprising awell according to an embodiment of the invention. Using FIGS. 5a and 5 bfor reference, the illustrated device 100 comprises a well 50 comprisinga hollow tube, and a filter 20 having an upper surface 21 and a lowersurface 22 (the filter comprising a filter element 25), interposedbetween a sealing ring 40 having a bottom surface 41, and a ribarrangement 5 having an top surface 6, wherein the lower surface 22 ofthe filter contacts the top surface 6 of the rib arrangement, and theupper surface 21 of the filter contacts the bottom surface 41 of thesealing ring. The hollow tube comprises a side wall 10 having an axis,the side wall 10 having an inner surface 2, the well having a top (orupper) end 1, and a bottom (or lower) end 3, wherein the ends areaxially spaced, the bottom end 3 comprising a bottom wall 4 and a fluidflow port 7, and a rib arrangement 5 projecting upwardly from the bottomwall.

[0061] In the embodiment shown in FIG. 5b, the rib arrangement 5 has araised portion such as a rib, ridge, or boss, and has a top surface 6(that is preferably a non-planar surface, e.g., a rounded surface)disposed to contact the lower surface 22 of a filter 20 comprising atleast one filter element 25. As will be described in more detail below(e.g., with reference to FIG. 16), in other embodiments of the ribarrangement, the arrangement has a surface disposed to contact the uppersurface of a filter.

[0062] The top surface 6 of the rib arrangement illustrated in FIGS. 5aand 5 b does not contact the inner surface 2 of the side wall of thewell (the Figures show a depression between the top surface of the ribarrangement and the inner surface of the side wall), and the ribarrangement can be located a predetermined distance from the innersurface of the side wall. In this illustrated embodiment, a sealing ring40 having a bottom surface 41, a top surface 42, and an outer surface43, is retained against the inner surface of the hollow tubular wall,the outer surface 43 of the ring pressing against the inner surface 2 ofthe side wall (e.g., at location 30, that can be a predeterminedposition along the inner surface of the wall), and the lower surface 41of the ring pressing against the upper surface 21 of the filter 20 whilethe top surface 6 of the rib arrangement 5 presses against the lowersurface 22 of the filter. The sealing ring 40 efficiently seals thefilter 20 in the well, typically by compressing the portion of thefilter surface contacting the sealing ring lower surface 41 as theportion of the filter surface contacting top surface 6 is alsocompressed. Thus, fluid is prevented from bypassing the filter (i.e.,passing around the edges of the filter rather than through the filter).Accordingly, fluid passes from the upper surface of the filter throughthe lower surface of the filter, and passes from the well through flowport 7.

[0063] Typically, the device, and more typically, the well, includes oneor more additional components for more efficient fluid processing, e.g.,to prevent masking or blocking of the filter. For example, using theillustrative embodiments shown in FIGS. 3, 8, 13, and 17 (describedbelow) for reference, the bottom end can include a drainage gridcomprising one or more spacers and/or channels arranged such that fluidpassing through the filter passes along the drainage channels betweenthe grid spacers and then through the fluid flow port.

[0064] In a preferred embodiment, the bottom end comprises a drainagegrid comprising at least one, more preferably, at least two, and evenmore preferably, at least three, drainage grid spacers projectingupwardly from the bottom wall. Illustratively, as shown in FIG. 5a (cutaway view), and shown in more detail in FIG. 3 (top view), the bottomend 3 comprises a drainage grid 80 comprising a drainage grid wall 85 (aportion of bottom wall 4), drainage grid spacers 81 a-d, 83 a-d and 84a-d projecting upwardly from bottom wall 4, and drainage channelsbetween the grid spacers (the drainage grid wall 85 forming the bottomof the drainage channels), wherein the drainage channels communicatewith fluid flow port 7. Drainage grid spacers 81 a-d, 83 a-d, and 84a-d, have top surfaces 82 a-d, 86 a-d, and 87 a-d, respectively.

[0065] The drainage grid can have a variety of configurations so long asthe filter can be supported and sufficient space is allowed for thepassage of filtrate. For example, in one embodiment (not shown), thespacers and/or channels can have a radial and/or circular configuration.Additionally, or alternatively, the drainage grid wall, the drainagechannels and/or the drainage grid spacers can have, for example, aconfiguration sloping toward the fluid flow port 7. Fluid flow port 7can have a tapered configuration if desired.

[0066] In some embodiments, e.g., using the embodiment illustrated inFIG. 2 for reference, the top surfaces of the drainage grid spacers(e.g., top surfaces 82 a and 82 c, that can be planar or non-planar) aresubstantially coplanar with the bottom wall 4 between the ribarrangement 5 and the inner surface 2 of the tube. If desired, thisportion of the bottom wall (between the rib arrangement and the innersurface of the tube) can be substantially coplanar with the surface ofthe drainage grid wall 85, and other configurations can also besuitable.

[0067] The tubular wall is preferably cylindrical, but in someembodiments includes multiple sides, e.g., multiple flat sides in orderto provide a pentagonal, hexagonal, heptagonal, or octagonal shape, or acombination of flat and rounded portions.

[0068] While the tubular wall of the well can include a tapered section,e.g., a reduction in the inner diameter of the well along a portion ofthe length of the wall, the wall is preferably not tapered at thelocation where the sealing ring is retained against the inner surface ofthe side wall.

[0069] The sealing ring is preferably arranged to be frictionallyengaged against the inner surface of the side wall. Since the tubularwall is preferably cylindrical, the sealing ring 40 preferably comprisesa generally annular ring, the sealing ring having an axis, and an outersurface 43.

[0070] In the embodiment illustrated in FIGS. 4b, 5 a and 5 b, thesealing ring also comprises a bottom surface 41. More preferably, thebottom surface 41 has a width dimension radially of the ring that isgenerally the same as the radial width of the top surface 6 of thecircumferential rib arrangement 5. Since the sealing ring 40 ispreferably frictionally engaged against the inner wall of the well atposition 30, the outer surface 43 of the sealing ring before insertionin the well has a diameter that is larger than the inner diameter of thewall of the well at position 30, e.g., the outer diameter of the sealingring is compressed during insertion into the well. The ring, onceinserted into the well, is retained against the inner surface of thewall with the bottom surface 41 of the ring pressing against the uppersurface 21 of the filter 20, and pressing the peripheral portion of thelower surface 22 of the filter 20 against the top surface 6 of the ribarrangement 5. Accordingly, the filter can be efficiently secured andsealed in the well without utilizing welding and/or adhesives, e.g., tosecure the sealing ring in the well.

[0071] In accordance with some preferred embodiments of the invention,e.g., as described with respect to FIG. 5b above, and with respect toFIG. 6 below, clamping and sealing forces can be concentrated on theportion of the filter contacting the bottom surface of the sealing ringand the portion of the filter contacting the top surface of the ribarrangement. Clamping and sealing forces can be concentrated withrespect to the sealing ring and the rib arrangement in accordance withsome other embodiments of the invention (e.g., with respect to FIGS. 11and 16) as described in more detail below. In addition, since thesealing ring in accordance with each of these four embodiments ispreferably retained at a location in the well wherein the wall of thewell is not tapered, the preferred configuration provides an efficientseal, keeps the filter substantially flat, and provides for maintainingthe seal during exposure to conditions (occurring, for example, duringshipping and/or storage) that could cause conventional seals to “backout” of the wells, e.g., conditions such as vibration and changes intemperature.

[0072] In these embodiments, the rib arrangement typically becomespartially deformed when the seal is created in accordance with theinvention. Since there is a range of achievable deformation whileproviding efficient sealing, the rib arrangement compensates for somevariability in, for example, the filters and/or the plates (e.g., withrespect to thickness and/or flatness) of the devices. Additionally, inthose embodiments including a plurality of separate inserts (e.g., asshown in FIGS. 12 and 18), the use of separate inserts allows the sealto be optimized with respect to individual wells and/or a series ofwells, that also compensates for variability in the filters and/orplates.

[0073] The sealing ring can be made of any suitable material thatprovides a desired property or combination of properties, such as, forexample, resilience, chemical compatibility with the sample or reactioncomponents, and cost. Exemplary materials include, but are not limitedto, rubber, silicone, and thermoplastic materials such as, for example,polypropylene and polystyrene.

[0074] As noted above, the device can have additional components. Forexample, the embodiment of the device illustrated in FIG. 5b includes anoutlet 200 (e.g., forming a nozzle) communicating with fluid flow port7. The outlet can have any suitable dimension and/or configuration. Ifdesired, the outlet can be arranged to further reduce undesired liquidloss from the well caused by capillary action and/or gravity flow(sometimes referred to as “wicking”). For example, the outlet caninclude a shoulder or collar preventing liquid from migrating upwardlyalong the outer diameter of the outlet. Alternatively, or additionally,the outlet can, for example, have any desired length. Illustratively, inthe embodiment shown in FIG. 5b, the tip of the outlet does not extendto the bottom surface of plate 101. In other embodiments, e.g., as shownin FIGS. 6, 11, and 16, the tip of the outlet extends beyond the bottomsurface of plate 101 (FIG. 6), or plate 102 (FIGS. 11 and 16).Typically, a longer outlet (e.g., as shown in FIGS. 6, 11 and 16) isdesirable for those applications wherein the filtrate is to be analyzed,and the tip of the outlet will extend into a receiving plate during use.Alternatively, a shorter outlet (e.g., as shown in FIG. 5b) can bedesirable for those applications wherein the retentate (the materialretained in the well) is to be analyzed, as the tip of the outlet willnot contact the surface of, for example, the lab bench when the plate101 is placed on the lab bench. Thus, the potential for contamination ofthe work area and/or the filtrate can be reduced.

[0075] A plurality of wells can be connected together, e.g., in the formof a strip, disc, sheet, or tray. In preferred embodiments, a pluralityof wells are connected together for use in devices according to theinvention. For example, FIGS. 1, 7 and 14 show portions of embodimentsof devices providing 96 well and 384 well devices. In anotherillustrative embodiment (not shown) a plurality of wells connected inthe form of one or more strips can be attached (e.g., by a snap fit) toa support, frame, or plate. Alternatively, or additionally, e.g., in avariation of the embodiments shown in FIGS. 11 and 16, a plurality ofinserts are connected together, for example, in the form of a strip,disc, sheet, or tray.

[0076] In some embodiments of the invention, especially some embodimentsof multiple well devices according to the invention, the devicecomprises at least one plate or tray defining at least a part of theupper portion of the wells or at least a part of the lower portion ofthe wells (the plate or tray can comprise the sealing ring); a pluralityof separate components (preferably inserts) defining at least a part ofanother portion of the well (e.g., a part of the lower portion whereinthe plate or tray defines at least a part of the upper portion of thewells; and the separate insert can further comprise the sealing ring),and a filter compressed by the sealing ring. In other embodiments ofmultiple well devices, the device comprises at least a top plate and abottom plate, and a filter. For example, the device can comprise anupper plate or tray defining the upper portion of the wells and/or thesealing ring, a bottom plate or tray defining at least the bottom wallof the wells, and a filter between the sealing ring and the bottom wall.Typically, the plates and/or separate components are snap-fit orpress-fit together. In some embodiments, the plates and/or separatecomponents are snap-fit or press-fit together and subsequentlyadditionally bonded, e.g., via welding (such as ultrasonic welding),adhesives and/or solvents.

[0077] In accordance with the embodiment illustrated in partialcross-sectional view in FIG. 6, multiple well device 100 comprises a topplate 102 comprising sealing rings 40, a bottom plate 101 comprisingbottom walls 4, and filters 20 each comprising at least one filterelement 25, between the sealing rings and the bottom walls. The Figureshows two wells 50 (one well in exploded view), each well including afilter 20 comprising at least one filter element 25. The bottom plate101 comprises (for each well) a side wall 10 having an inner surface 2,bottom end 3 comprising a bottom wall 4, a rib arrangement 5 and a fluidflow port 7, and a top plate 102 comprises (for each well) a sealingring 40 having a bore 45. In the illustrated assembled well, the filteris compressed between the bottom surface 41 of the sealing ring and thetop surface 6 of the rib arrangement.

[0078] As with the embodiment illustrated in FIGS. 1-5, the ribarrangement 5 illustrated in FIG. 6 has a top surface 6 (that ispreferably a non-planar surface) disposed to contact the lower surface22 of the filter 20 comprising at least one filter element 25. The topsurface 6 of the rib arrangement does not contact the inner surface 2 ofthe side wall of the well, and the rib arrangement can be located apredetermined distance from the inner surface of the side wall.

[0079] In accordance with the embodiment illustrated in FIG. 6, whereinthe top plate 102 comprises a sealing ring 40, the ring, having a bottomsurface 41, and an outer surface 43, is retained against the innersurface of the hollow tubular wall, the outer surface 43 of the ringpressing against the inner surface 2 of the side wall (e.g., at location30), and the lower surface 41 of the ring pressing against the uppersurface 21 of the filter 20 while the top surface 6 of the ribarrangement 5 presses against the lower surface of the filter. In thisembodiment, as with the embodiments illustrated in FIGS. 1-5, since thesealing ring 40 efficiently seals the filter 20 in the well, fluid isprevented from bypassing the filter.

[0080] FIGS. 7-10 illustrate the individual components of the multiplewell device 100 including the assembled well 50 shown in FIG. 6.Accordingly, FIG. 7 shows a top view of the bottom plate 101, showingthe bottom ends of a plurality of wells, and FIG. 8 shows a top view ofthe bottom end of a well in more detail, wherein the end 3 includes abottom wall 4, a rib arrangement 5 projecting upwardly from the bottomwall, a drainage grid 80 comprising a plurality of drainage grid spacers81 a-d projecting upwardly from the drainage grid wall 85 (a portion ofbottom wall 4), and a fluid flow port 7. However, in other embodimentsof the invention, the lower portion of the wells can have differentarrangements, e.g., as shown in FIGS. 1 and 3, as well as FIGS. 13 and17 (described below).

[0081]FIGS. 9 and 10a show, respectively, a top view, and a-partialcross-sectional view of the top plate 102 shown in FIG. 6, and FIG. 10bshows a partial cross-sectional view of the bottom plate 101. As shownin more detail in FIG. 10a, top plate 102 comprises a sealing ring 40having a bore 45, the ring having an outer surface 43 and a lowersurface 41. The outer surface 43 of the ring presses against (as shownin FIG. 6) the inner surface 2 of the side wall of the tube 10 in thebottom plate 101.

[0082] In the embodiment illustrated in FIGS. 6 and 10a, the sealingring 40 has a bore 45, and the bore extends to the top surface of thetop plate. The bore is suitable for receiving fluid, and typically(using FIG. 6 for reference), fluid does not contact the inner surface 2of the side wall 10. This is in contrast with, for example, theembodiments illustrated in FIGS. 5, 11 and 16, wherein fluid can contactthe inner surface 2.

[0083] Embodiments of devices according to the invention can include aseparate sealing ring (e.g., as shown in FIG. 5), or a sealing ring aspart of an upper portion of the device (e.g., top plate 102 as shown inFIGS. 6 and 10a), or a sealing ring as part of the lower portion of thedevice, e.g., as part of the inserts described with respect to FIGS. 11and 16 below.

[0084] In accordance with the embodiment illustrated in partialcross-sectional view in FIG. 11 (showing an assembled well and anexploded view of a well), multiple well device 100 comprises a top plate102 having a plurality of wells 50, each well comprising a side wall 10having an inner surface 2, an inwardly extending lip 70 having a lowersurface 71 (the lip, typically an annular member, e.g., a ledge orflange, and the side wall, can be injection molded as a unitary piece);and a bottom chamber 103 (preferably a separate insert, typicallyforming a nozzle) comprising a bottom end 3 comprising a bottom wall 4,the bottom end also comprising a sealing ring 40 comprising a ribarrangement 5 having a top surface 6 projecting upwardly from the bottomwall, a grid arrangement 80, and a fluid flow port 7; and a filter 20comprising at least one filter element 25, compressed between the topsurface 6 of the rib arrangement 5 (the top surface of the sealing ring)and the lower surface 71 of the lip.

[0085] In the embodiment illustrated in FIG. 11, the sealing ring 40comprises an outer surface 43, and the rib arrangement 5 wherein the topsurface 6 of the rib arrangement provides the top surface of the sealingring. The top surface 6 (that is preferably a non-planar surface) isdisposed to contact the lower surface 22 of the filter 20 comprising atleast one filter element 25. Typically, the top surface 6 of the ribarrangement does not contact the inner surface 2 of the side wall of thewell, and the rib arrangement can be located a predetermined distancefrom the inner surface of the side wall, e.g., a predetermined distancefrom that portion of the inner surface (portion 2 a of inner surface 2)below the lower surface 71 of lip 70. Preferably, the top surface of therib arrangement has a radial width that is at least the radial width ofthe lower surface of the lip.

[0086] In sealing the filter in the device illustrated in FIG. 11, theouter surface 43 of the sealing ring presses against the inner surface 2of the side wall, and the lower surface of the lip presses against aportion of the upper surface 21 of the filter 20 (e.g., at least theportion of the upper surface 21 opposite the portion of the lowersurface of the filter contacting the top of the rib arrangement) whilethe top surface 6 of the rib arrangement 5 presses against the lowersurface 22 of the filter. As with the other embodiments, fluid isprevented from bypassing the filter.

[0087] FIGS. 12-15 illustrate the individual components of the multiplewell device 100 shown in FIG. 11. Accordingly, FIGS. 12 (partial cutaway view) and 13 (top view) show the bottom chamber 103, comprising thebottom end 3 including a bottom wall 4, sealing ring 40 comprising anouter surface 43 and a rib arrangement 5 projecting upwardly from thebottom wall, a drainage grid 80 comprising a plurality of drainage gridspacers 81 a-d projecting upwardly from the bottom wall 4, and a fluidflow port 7. FIGS. 14 and 15 show, respectively, a top view, and apartial cross-sectional view of the top plate 102 shown in FIG. 11.

[0088]FIG. 16 shows a partial cross-sectional view of another embodimentof a multiple well device according to the invention (showing anassembled well and an exploded view of a well), and FIGS. 17-19illustrate individual components of this embodiment of the device inmore detail.

[0089]FIG. 16 shows multiple well device 100 comprising a top plate 102having a plurality of wells 50, each well comprising a side wall 10having an inner surface 2, an inwardly extending lip 70 comprising a ribarrangement 5 projecting downwardly from the lip, the lip having abottom surface 6 a, preferably spaced away from the inner surface 2 ofthe side wall. The lip and side wall can be injection molded as aunitary piece. FIG. 16 also shows a bottom chamber 103 (preferably aseparate insert, more typically forming a nozzle) comprising a bottomend 3 comprising a bottom wall 4, the bottom end also comprising a gridarrangement 80, and a fluid flow port 7, and a sealing ring 40comprising an outer surface 43 and a top surface, wherein the bottomwall of the bottom end comprises the top surface of the sealing ring,and a filter 20 comprising at least one filter element 25, compressedbetween the bottom surface 6 a of the rib arrangement 5 and the topsurface of the sealing ring.

[0090] FIGS. 17-19 illustrate the individual components of the multiplewell device 100 shown in FIG. 16. Accordingly, FIGS. 17 (top view) and18 (partial cut away view) show the bottom chamber 103, comprising thebottom end 3 including a bottom wall 4, sealing ring 40 comprising anouter surface 43 and a top surface, wherein the bottom wall of thebottom end comprises the top surface of the sealing ring, a drainagegrid 80 comprising a plurality of drainage grid spacers 81 a-dprojecting upwardly from the bottom wall 4, and a fluid flow port 7.FIG. 19 shows a partial cross-sectional view of the top plate 102 shownin FIG. 16, including side wall 10 having an inner surface 2, aninwardly extending lip 70 comprising a rib arrangement 5 projectingdownwardly from the lip, the lip having a bottom surface 6 a. In thisillustrated embodiment, the bottom surface 6 a is spaced away from theinner surface 2 of the side wall (e.g., the Figure shows a depressionbetween the bottom surface 6 a and portion 2 a of inner surface 2).Preferably, the bottom surface 6 a of the rib arrangement has a radialwidth that is at least the radial width of the top surface of thesealing ring.

[0091] In sealing the filter in the device shown in FIG. 16, the outersurface 43 of the sealing ring presses against the inner surface 2 ofthe side wall 10 (at portion 2 a), and the bottom surface 6 a of the ribarrangement 5 presses against a portion of the upper surface 21 of thefilter 20 while the top surface of the sealing ring presses against thelower surface 22 of the filter. As with the other embodiments, fluid isprevented from bypassing the filter.

[0092] In a variation of the embodiment illustrated in FIGS. 17-19, theinwardly extending lip does not include a rib arrangement projectingdownwardly from the lip. For example, the lip can have a lower surface,and the lower surface presses against a portion of the upper surface ofthe filter while the top surface of the sealing ring presses against thelower surface of the filter.

[0093] As described above with respect to embodiments of the invention,the sealing ring 40 is preferably frictionally engaged against the innerwall of the well, while providing for sealing the filter in the wellwithout requiring the use of welding and/or adhesives to retain the ringin the well. For example, using the embodiments illustrated in FIGS. 5band 6 for reference, the sealing ring is frictionally engaged againstthe wall at location 30, with the bottom surface 41 of the ring pressingagainst the upper surface 21 of the filter 20, and the peripheralportion of the lower surface 22 of the filter 20 pressing against thetop surface 6 of the rib arrangement 5. The sealing ring can also befrictionally engaged against the wall at position 30 as shown in theembodiments illustrated in FIGS. 11 and 16. If desired, position 30 canbe predetermined, e.g., by adjusting the thickness and/or density of thefilter elements. Alternatively, or additionally, the position can bepredetermined by controlling the force applied to introduce the sealingring into the hollow tube (FIG. 5) or the force applied to introduce theinserts into the trays (e.g., introducing the inserts comprising sealingrings into the top plates using FIGS. 11 and 16 for reference). Thefrictional engagement is preferably accomplished by adjusting therelative sizes of the outer diameter of the sealing ring and the innerdiameter of the well.

[0094] A variety of materials are suitable for producing ribarrangements, lips, drainage grids, inserts, chambers, plates, andsealing rings according to the invention. Illustrative materialsinclude, for example, polyvinyl chloride with or without copolymers,polyethylenes, polystyrenes, polystyrene-acrylonitrile, polypropylene,polyvinylidine chloride, and the like.

[0095] The wells and multiple well devices according to the inventioncan have any suitable overall dimension and capacity, although preferredembodiments have substantially the same overall dimension and capacityof standard wells and devices. Such embodiments are preferred as beingmore easily utilized with devices and instruments, such as liquidhandling systems and readers, that are commonly available for use withconventional wells and devices. In those applications wherein a signalis generated, e.g., in the course of a microtitration assay, the signalcan be read by any suitable means, e.g., by visual analysis, or thedetection of a fluorometric, spectrophotometric, radiometric, orchemiluminescent signal.

[0096] Typically, each well is suitable for receiving at least about 200microliters (μL), more typically, at least about 350 μL, of fluid to beprocessed. In some embodiments, each well is suitable for receiving atleast about 800 μL of fluid, or at least about 1 mL, or at least about 2mL of fluid, or more.

[0097] If desired, the well, more typically, a multiple well device, ischemically resistant, and can be used with harsh solvents and/or harshchemicals.

[0098] The present invention is useful in a variety of applicationsincluding microtitration, microchromatography, radiography,microfiltration, ultrafiltration, nanofiltration, washing processes,polymerase chain reaction (PCR) analysis, high throughput, especiallyhigh throughput screening (HTS), combinatorial chemistry, nucleic acidand protein processing (including synthesis, sequencing, separationand/or purification) and microculture of cell suspensions and tissues.The invention can be used in any suitable setting, including, but notlimited to, hospitals and laboratories. Embodiments of the invention aresuitable for a variety of protocols, including sample preparation,clinical diagnostic assays, and screening specimens, e.g., drugs inpharmaceutical research. If desired, materials (e.g., ligands, nucleicacids) can be bound to solid phase particles such as beads and collectedin the wells, and the materials can be cleaved from the particles suchthat the materials are collected in the filtrate. In some embodiments,the cleaved materials (e.g., ligands and synthesized nucleic acids) canbe further processed (e.g., screened) using another well, e.g., thefiltrate can be passed into one or more multiple well devices.Alternatively, or additionally, the invention can be compatible withother subsequent processes including, but not limited to, at least oneof dot blotting, immunoblotting, receptor binding assays, ELISA, andRIA.

[0099] Embodiments of the invention are especially suitable for removingparticulates from a fluid, e.g., to provide a filtered sample foranalysis, for example, by high pressure liquid chromatography (HPLC),gas chromatography (GC), mass spectrometry (MS), infra red (IR), nuclearmagnetic resonance (NMR), and solid-phase extraction.

[0100] Accordingly, a variety of filters and filter elements (as usedherein, the terms “filter” and “filter element” refer to porous mediaused in these various applications) are suitable for use in theinvention, and those skilled in the art will recognize that the choiceof filter(s) and filter element(s) will depend on the intended use ofthe well. The filter can comprise a depth filter and/or a sieve filter.The filter can include fibrous and/or membrane filter elements. Thefilter can include additional elements and/or components such as, forexample, at least one of a drainage, cushion, and prefilter layer.Typical filter elements include membranes, especially polymericmembranes. For some applications, the filter elements are chemicallyresistant, and can be used with harsh solvents and/or harsh chemicals.In some embodiments, the filter comprises a plurality of filterelements, and the elements can have different characteristics, e.g., atleast one of pore size, chemistry (for example, at least one of criticalwetting surface tension, surface charge, polarity, hydrophilicity, andattached functional groups), and can include different reagents andassay components.

[0101] Filters and filter elements of suitable shape for use in theinvention are typically stamped or otherwise cut out of sheets ofsuitable material(s), e.g., membrane sheets.

[0102] A filter element such as a porous membrane or a fibrous elementcan have any suitable pore structure such as a pore size, or a porerating or a pore diameter. Thus, e.g., a filter element comprising amembrane typically has an average pore size of about 100 μm or less,preferably from about 0.01 μm to about 100/m. In some embodiments, themembrane has an average pore size of about 0.1 μm or less, or from about0.1 μm to about 10 μm. Preferably, the membrane has an average pore sizeof about 5 μm or less.

[0103] All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference to the sameextent as if each reference were individually and specifically indicatedto be incorporated by reference and were set forth in its entiretyherein.

[0104] The use of the terms “a” and “an” and “the” and similar referentsin the context of describing the invention (especially in the context ofthe following claims) are to be construed to cover both the singular andthe plural, unless otherwise indicated herein or clearly contradicted bycontext. Recitation of ranges of values herein are merely intended toserve as a shorthand method of referring individually to each separatevalue falling within the range, unless otherwise indicated herein, andeach separate value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (e.g., “such as”) provided herein, isintended merely to better illuminate the invention and does not pose alimitation on the scope of the invention unless otherwise claimed. Nolanguage in the specification should be construed as indicating anynon-claimed element as essential to the practice of the invention.

[0105] Preferred embodiments of this invention are described herein,including the best mode known to the inventors for carrying out theinvention. Of course, variations of those preferred embodiments willbecome apparent to those of ordinary skill in the art upon reading theforegoing description. The inventors expect skilled artisans to employsuch variations as appropriate, and the inventors intend for theinvention to be practiced otherwise than as specifically describedherein. Accordingly, this invention includes all modifications andequivalents of the subject matter recited in the claims appended heretoas permitted by applicable law. Moreover, any combination of theabove-described elements in all possible variations thereof isencompassed by the invention unless otherwise indicated herein orotherwise clearly contradicted by context.

What is claimed is:
 1. A well for use in processing a fluid comprising:a hollow tube having an axis, the tube comprising a side wall having aninner surface; upper and lower axially spaced ends, the lower endcomprising a bottom wall and a fluid flow port, and a rib arrangementprojecting upwardly from the bottom wall, the rib arrangement having atop surface spaced from the inner surface of the side wall; a sealingring having an outer surface, and a bottom surface, the outer surface ofthe sealing ring pressing against the inner surface of the side-wall ofthe tube; a filter comprising at least one filter element, the filterhaving an upper surface and a lower surface, the filter being compressedbetween the bottom surface of the sealing ring and the top surface ofthe rib arrangement.
 2. The well of claim 1, wherein the bottom surfaceof the ring presses against the upper surface of the filter while thetop surface of the rib arrangement presses against the lower surface ofthe filter.
 3. The well of claim 1 or 2, wherein the lower end includesa drainage grid.
 4. A well for use in processing a fluid comprising: ahollow tube having an axis, the tube comprising a side wall having aninner surface and a lip extending inwardly from said side wall, the liphaving a lower surface; upper and lower axially spaced ends; the lowerend comprising a bottom wall and a fluid flow port and a sealing ring,the sealing ring comprising an outer surface and a top surface, theouter surface of the sealing ring pressing against the inner surface ofthe side wall of the tube; a filter comprising at least one filterelement, the filter having an upper surface and a lower surface, thefilter being compressed between the top surface of the sealing ring andthe lower surface of the lip.
 5. The well of claim 4, wherein thesealing ring further comprises a rib arrangement projecting upwardlyfrom the bottom wall, the rib arrangement having a top surface; whereinthe filter is compressed between the top surface of the rib arrangementand the lower surface of the lip.
 6. The well of claim 5, wherein thetop surface of the rib arrangement is spaced from the inner surface ofthe side wall.
 7. The well of claim 4, wherein the lip further comprisesa rib arrangement projecting downwardly from the lip, the ribarrangement having a bottom surface, and the filter is compressedbetween the top surface of the sealing ring and the bottom surface ofthe rib arrangement.
 8. The well of claim 7, wherein the bottom surfaceof the rib arrangement is spaced from the inner surface of the sidewall.
 9. The well of any of claims 4-8, wherein the lower end comprisesan insert.
 10. A multiple well device comprising: a plurality of wellseach having an upper end and a lower end and a filter, wherein a topplate comprises the upper ends of the plurality of wells; a plurality ofseparate inserts comprising the lower ends of the plurality of wells,each insert comprising a bottom wall and a fluid flow port and aplurality of filters, each filter comprising at least one filterelement, wherein each filter is sealed between the top plate and aninsert.
 11. The multiple well device of claim 10, wherein each insertincludes a sealing ring, the sealing ring having a surface disposed tocontact a lower surface of the filter.
 12. A multiple well devicecomprising: a plurality of wells for receiving liquid samples to beprocessed, each well having a side wall having an inner surface, abottom end comprising a bottom wall and a fluid flow port, and a ribarrangement projecting upwardly from the bottom wall, the ribarrangement having a top surface spaced from the inner surface of theside wall; a filter comprising at least one filter element in each well,the filter having an upper surface and a lower surface; and a sealingring sealing the filter against the rib arrangement, the sealing ringhaving an outer surface, and a bottom surface, the bottom surface havinga width that is at least the width of the top surface of the ribarrangement, the sealing ring pressing against the inner surface of theside wall, and the bottom surface of the ring pressing against the uppersurface of the filter while the top surface of the rib arrangementpresses against the lower surface of the filter.
 13. The well of any ofclaims 1-9, wherein the filter comprises a membrane.
 14. The well ofclaim 13, wherein the membrane comprises a microporous membrane.
 15. Thewell of claim 14, wherein the membrane comprises an ultrafiltrationmembrane.
 16. The well of any of claims 1-9, wherein the filtercomprises a fibrous medium.
 17. The well of any of claims 1-9 and 13-16,wherein the filter comprises at least two filter elements.
 18. The wellof any of claims 1-9 and 13-17, wherein the side wall is not taperedwhere the sealing ring presses against the inner surface of the sidewall.
 19. A multiple well device comprising: two or more wells accordingto any one of claims 1-9, and 13-18.
 20. The device of claim 19,comprising 96 wells.
 21. The device of claim 19, comprising 384 wells.22. A method for processing a fluid comprising: passing a fluid into adevice comprising a well comprising a side wall having an inner surface,and a bottom end having a rib arrangement having a top surface, whereinthe top surface of the rib arrangement is spaced from the inner surfaceof the side wall, and a fluid flow port; the well having a filtercomprising at least one filter element sealed therein, the filter beingcompressed between a lower surface of a sealing ring, and the topsurface of the rib arrangement; and, passing at least a portion of thefluid through the filter and through the fluid flow port at the bottomend of the well.
 23. A method for processing a fluid comprising: passinga fluid into a device comprising a well comprising a side wall having aninner surface, and a lip extending inwardly from said side wall, the liphaving a lower surface; and lower end comprising a bottom wall and afluid flow port and a sealing ring, the sealing ring comprising a topsurface; the well having a filter comprising at least one filter elementsealed therein, the filter being compressed between a lower surface ofthe lip, and the top surface of the sealing ring; and, passing at leasta portion of the fluid through the filter and through the fluid flowport at the bottom end of the well.
 24. The method of claim 22 or 23,wherein passing the fluid through the filter includes depleting thefluid of particulates.
 25. The method of any of claims 22-24, furthercomprising analyzing the fluid passing through the filter.